Water and heat management are the most critical issues for the performance of proton exchange membrane (PEM) fuel cells. They can be provided by keeping hydrogen flow rate, oxygen flow rate, cell temperature and humidification temperature under control. In this study, the effects of these parameters on the power density of proton exchange membrane (PEM) fuel cell which has 25 cm(2) active area have been examined experimentally using hydrogen on the anode side and oxygen on the cathode side. Response Surface Methodology (RSM) has been applied to optimize these operation parameters of proton exchange membrane (PEM) fuel cell. The test responses are the maximum output power density. ANOVA (analysis of variance) analyses are used to compute the effects and the contributions of the various factors to the fuel cell maximal power density. The use of this design shows also how it is possible to reduce the number of experiments. Hydrogen flow rate, oxygen flow rate, humidification temperature and cell temperature were the main parameters to have been varied between 2.5-5 L/min, 3-5 L/min, 40-70 degrees C and 40-80 degrees C in the analyses. The maximum power density was found as 241.977 mW/cm(2). Copyright (C) 2014, Hydrogen Energy Publications, LLC. Published by Elsevier Ltd. All rights reserved.